CIML NK Cell in Head & Neck Cancer

NCT04290546 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 19-505
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is evaluating the safety and efficacy of a combination drug and biologic therapy in patients with advanced head and neck cancer. This research study involves the following drugs and biologics:

• CIML NK donor cells
• IL-15 superagonist
• Ipilimumab
• Cetuximab

Conditions

Squamous Cell Carcinoma of the Head and Neck; Recurrent Head and Neck Squamous Cell Carcinoma

Keywords

Squamous Cell Carcinoma of the Head and Neck; Recurrent Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Rate of Dose Limiting Toxicity

  All patients receiving any dose of study treatment will be evaluated for safety. DLTs overall and by dose level will be reported as proportions with 90% exact binomial confidence intervals.

  first dose of study treatment up to 100 days

Secondary Outcomes (4)

• objective response rate (ORR)

  12 weeks

• complete response (CR) rate

  12 weeks

• disease-free survival (DFS)

  1 year

• overall survival (OS) at 1-year following infusion

  1 year

Study Arms (3)

Cohort I without Ipilimumab Lead in

EXPERIMENTAL

Haploidentical donor derived CIML NK cell infusion with subcutaneous N-803 for eligible patients with platinum-refractory and immune checkpoint blockade-refractory, advanced head and neck squamous cell carcinoma (Cohort 1) * CIML NK cell infusion (Dose 0 or -1) infused on Day 0. * Interleukin-15 Superagonist dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles).

Drug: Interleukin-15 Superagonist (N-803); Biological: CIML NK cell Infusion

Cohort 2 with Ipilimumab Lead In

EXPERIMENTAL

Cohort 2 treated with an ipilimumab lead-in prior to CIML NK cell infusion after safety is established with the NK cell and N-803 treatments alone. * Participants in the ipilimumab subgroup (Cohort 2) will receive a single dose of lead-in ipilimumab via iv per protocol determined dose followed by lymphodepleting chemotherapy on Day -6 for a total of 5-days, prior to receiving CIML NK cell infusion. * CIML NK cell infusion-Highest Dosed per cohort 1, infused on day 0 * Interleukin-15 Superagonist (N-803) Administration \-- dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles). * Cohort 2 will receive the highest number of CIML NK cells that is still considered safe and ipilimumab.

Drug: Interleukin-15 Superagonist (N-803); Biological: CIML NK cell Infusion; Drug: Ipilimumab

Cohort 3 with Cetuximab Infusions

EXPERIMENTAL

Cohort 3 treated with CIML NK cell infusion after safety is established with the NK cell and N-803 treatments alone, followed by cetuximab infusions. * \- Participants in cetuximab subgroup (Cohort 3) will receive lymphodepleting chemotherapy on Day -6 for a total of 5-days, prior to receiving CIML NK cell infusion. * CIML NK cell infusion-Highest Dosed per cohort 1, infused on day 0 * Interleukin-15 Superagonist (N-803) Administration \-- dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles). * Cetuximab Administration --dosed at 500mg/m2 IV over 120 minutes for the first dose, then over 60 minutes for subsequent doses. This will be infused every 14 days for 8 doses started on day +15. * Cohort 3 will receive the highest number of CIML NK cells that is still considered safe and ipilimumab.

Drug: Interleukin-15 Superagonist (N-803); Biological: CIML NK cell Infusion; Drug: Cetuximab

Interventions

Interleukin-15 Superagonist (N-803) DRUG

\-- Starting the day after (Cycle 1, Day +1) CIML NK-enriched cell infusion, at least 12 hours after CIML NK cell infusion is completed and up to 48 hours after CIML NK cell infusion, each participant will receive N-803 dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles). N-803 dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles) for cohorts 1 and 2, and 6 total doses in cohort 3. The dose should be calculated based on body weight at study entry, and recalculated only if greater than 10% change in weight.

Cohort 2 with Ipilimumab Lead In; Cohort 3 with Cetuximab Infusions; Cohort I without Ipilimumab Lead in

CIML NK cell Infusion BIOLOGICAL

(Dose 0 or -1) infused on Day 0

Also known as: cytokine induced memory-like natural killer

Cohort 2 with Ipilimumab Lead In; Cohort 3 with Cetuximab Infusions; Cohort I without Ipilimumab Lead in

Ipilimumab DRUG

single dose of lead-in ipilimumab via iv per protocol determined dose

Also known as: CTLA-4 inhibitor

Cohort 2 with Ipilimumab Lead In

Cetuximab DRUG

Starting day +15, every 14 days for 8 total doses via IV per protocol

Also known as: EGFR inhibitor

Cohort 3 with Cetuximab Infusions

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed, recurrent or metastatic squamous cell carcinoma of the head neck (including oral cavity, oropharynx, larynx, hypopharynx, paranasal sinuses) or salivary gland carcinoma (including adenoid cystic carcinoma and non-adenoid cystic carcinoma histologies)
• Any HPV status or smoking history is permitted. Oropharyngeal cancer patients are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV PCR or ISH testing
• Available haploidentical donor that is willing and eligible for non-mobilized collection
• Prior exposure to a platinum-containing regimen (either in the definitive or advanced, recurrent/metastatic setting) and exposure to a PD-1/L1 inhibitor is required for SCCHN patients only
• Age 18 years or older
• ECOG performance status ≤ 2 (see Appendix A).
• No systemic corticosteroid therapy (≤ 10 mg of prednisone or equivalent dose of systemic steroids for non-autoimmune indications for at least 4 weeks prior to NK cell infusion).
• Ability to understand and the willingness to sign a written informed consent document.
• Negative pregnancy test for women of childbearing potential only. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab.
• The effects of CIML NK cells and N-803 on the developing human fetus are unknown.
• For this reason, WOCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for up to 26 weeks after the last dose of all investigational products (up to 16 weeks after the last N-803 dose), in such a manner that the risk of pregnancy is minimized. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Willing to provide blood and tissue from diagnostic biopsy and at the time of surgery
• Participants must have normal organ and marrow function as defined below:
• leukocytes ≥ 2,500/mcL
• absolute neutrophil count ≥ 1,000/mcL

You may not qualify if:

• Patients with nasopharyngeal carcinoma are not eligible
• Participants who have had anti-tumor chemotherapy or other investigational agents within 2 weeks prior to cell infusion (6 weeks for nitrosoureas or mitomycin C), or immunotherapy within 3 weeks prior, or those who have not recovered from adverse events due to agents administered more than 3 weeks prior.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to N-803 or other agents used in study.
• Solid organ transplant (allograft) recipients.
• Participants who are receiving any other investigational agents.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[Wegener's granulomatosis\]) and motor neuropathy considered of autoimmune origin (e.g. Guillain- Barre syndrome and myasthenia gravis). Patients with Hashimoto thyroiditis are eligible.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because of the unknown teratogenic risk of CIML NK cells and N-803 and with the potential for teratogenic or abortifacient effects by fludarabine/cyclophosphamide chemotherapy regimen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CIML NK cells and N-803, breastfeeding should be discontinued if the mother is treated on this study.
• HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions with anti-retroviral agents used in this study. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high-risk of lethal treatment-related hepatotoxicity in the setting of marrow suppression.
• Known non-infectious pneumonitis or any history of interstitial lung disease.
• Receipt of a live vaccine within 30 days of start of study treatment.

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: collaborator
• Dana-Farber Cancer Institute: lead
• Altor BioScience: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Shapiro RM, Sheffer M, Booker MA, Tolstorukov MY, Birch GC, Sade-Feldman M, Fang J, Li S, Lu W, Ansuinelli M, Dulery R, Tarannum M, Baginska J, Dwivedi N, Kothari A, Penter L, Abdulhamid YZ, Kaplan IE, Khanhlinh D, Uppaluri R, Redd RA, Nikiforow S, Koreth J, Ritz J, Wu CJ, Soiffer RJ, Hanna GJ, Romee R. First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer. J Hematol Oncol. 2025 Feb 14;18(1):17. doi: 10.1186/s13045-025-01669-3.

  PMID: 39948608 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

ALT-803; Ipilimumab; Immune Checkpoint Inhibitors; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Glenn Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: March 2, 2020
• Study Start: July 20, 2020
• Primary Completion: September 1, 2024
• Study Completion: December 16, 2024
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)